PT - JOURNAL ARTICLE AU - Nadine Schweizer AU - Thomas Viereckel AU - Casey J.A. Smith-Anttila AU - Karin Nordenankar AU - Emma Arvidsson AU - Souha Mahmoudi AU - André Zampera AU - Hanna Wärner Jonsson AU - Jonas Bergquist AU - Daniel Lévesque AU - Åsa Konradsson-Geuken AU - Malin Andersson AU - Sylvie Dumas AU - Åsa Wallén-Mackenzie TI - Reduced <em>Vglut2/Slc17a6</em> Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption AID - 10.1523/ENEURO.0264-16.2016 DP - 2016 Sep 01 TA - eneuro PG - ENEURO.0264-16.2016 VI - 3 IP - 5 4099 - http://www.eneuro.org/content/3/5/ENEURO.0264-16.2016.short 4100 - http://www.eneuro.org/content/3/5/ENEURO.0264-16.2016.full SO - eNeuro2016 Sep 01; 3 AB - The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson’s disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system.